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Acute Respiratory Infections (Update September 2009)

References

[1] World Health Organization. Changing history. Geneva 2004.

[2] Kieny MP, Girard MP. Human vaccine research and development: an overview. Vaccine 2005;23:5705-7.

[3] Mizgerd JP. Lung infection--a public health priority. PLoS Med 2006;3:e76.

[4] Williams BG, Gouws E, Boschi-Pinto C, Bryce J, Dye C. Estimates of world-wide distribution of child deaths from acute respiratory infections. Lancet Infect Dis 2002;2:25-32.

[5] Scott JA, Brooks WA, Peiris JS, Holtzman D, Mulhollan EK. Pneumonia research to reduce childhood mortality in the developing world. J Clin Invest 2008;118:1291-300.

[6] Rudan I, Boschi-Pinto C, Biloglav Z, Mulholland K, Campbell H. Epidemiology and etiology of childhood pneumonia. Bull World Health Organ 2008;86:408-16.

[7] Walter ND, Grant GB, Bandy U, Alexander NE, Winchell JM, Jordan HT, et al. Community outbreak of Mycoplasma pneumoniae infection: school-based cluster of neurologic disease associated with household transmission of respiratory illness. J Infect Dis 2008;198:1365-74.

[8] Chandran A, Watt JP, Santosham M. Haemophilus influenzae vaccines. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines 5th ed: Saunders-Elsevier, 2008: 155-76.

[9] WHO position paper on Haemophilus influenzae type b conjugate vaccines. (Replaces WHO position paper on Hib vaccines previously published in the Weekly Epidemiological Record. Wkly Epidemiol Rec 2006;81:445-52.

[10] World Health Organization. Make any mother and child count. Geneva; 2005.

[11] Jackson LA, Neuzil KM. Pneumococcal polysaccharide vaccines. In: Plotkin SA, Orestein WA, Offit PA, editors. Vaccines 5th ed: Saunders-Elsevier, 2008: 569-604.

[12] World Health Organization. Proceedings of the 7th Global Vaccine Research Forum IVR. Bangkok Thailand; 2006 3-6 December.

[13] Metlay JP, Fishman NO, Joffe M, Edelstein PH. Impact of pediatric vaccination with pneumococcal conjugate vaccine on the risk of bacteremic pneumococcal pneumonia in adults. Vaccine 2006;24:468-75.

[14] Progress in reducing global measles deaths: 1999-2002. Wkly Epidemiol Rec 2004;79:20-1.

[15] Muller CP, Kremer JR, Best JM, Dourado I, Triki H, Reef S. Reducing global disease burden of measles and rubella: report of the WHO Steering Committee on research related to measles and rubella vaccines and vaccination, 2005. Vaccine 2007;25:1-9.

[16] Karron RA. Respiratory synsytial virus and parainfluenza virus vaccines. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines 5th ed: Saunders- Elsevier, 2008: 1283-93.

[17] Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA 1999;282:1440-6.

[18] Weber MW, Mulholland EK, Greenwood BM. Respiratory syncytial virus infection in tropical and developing countries. Trop Med Int Health 1998;3:268-80.

[19] Han LL, Alexander JP, Anderson LJ. Respiratory syncytial virus pneumonia among the elderly: an assessment of disease burden. J Infect Dis 1999;179:25-30.

[20] Xepapadaki P, Psarras S, Bossios A, Tsolia M, Gourgiotis D, Liapi-Adamidou G, et al. Human Metapneumovirus as a causative agent of acute bronchiolitis in infants. J Clin Virol 2004;30:267-70.

[21] Foulongne V, Guyon G, Rodiere M, Segondy M. Human metapneumovirus infection in young children hospitalized with respiratory tract disease. Pediatr Infect Dis J 2006;25:354-9.

[22] Wolf DG, Greenberg D, Kalkstein D, Shemer-Avni Y, Givon-Lavi N, Saleh N, et al. Comparison of human metapneumovirus, respiratory syncytial virus and influenza A virus lower respiratory tract infections in hospitalized young children. Pediatr Infect Dis J 2006;25:320-4.

[23] Mazzoncini JP, Jr., Crowell CB, Kang CS. Human metapneumovirus: An emerging respiratory pathogen. J Emerg Med 2008.

[24] Lau SK, Woo PC, Yip CC, Tse H, Tsoi HW, Cheng VC, et al. Coronavirus HKU1 and other coronavirus infections in Hong Kong. J Clin Microbiol 2006;44:2063-71.

[25] Kahn JS. The widening scope of coronaviruses. Curr Opin Pediatr 2006;18:42-7.

[26] van der Hoek L. Human coronaviruses: what do they cause? Antivir Ther 2007;12:651-8.

[27] Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 2003;300:1394-9.

[28] Snijder EJ, Bredenbeek PJ, Dobbe JC, Thiel V, Ziebuhr J, Poon LL, et al. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol 2003;331:991-1004.

[29] Peiris JS, Guan Y, Yuen KY. Severe acute respiratory syndrome. Nat Med 2004;10:S88-97.

[30] Zhou T, Wang H, Luo D, Rowe T, Wang Z, Hogan RJ, et al. An exposed domain in the severe acute respiratory syndrome coronavirus spike protein induces neutralizing antibodies. J Virol 2004;78:7217-26.

[31] Zhang H, Wang G, Li J, Nie Y, Shi X, Lian G, et al. Identification of an antigenic determinant on the S2 domain of the severe acute respiratory syndrome coronavirus spike glycoprotein capable of inducing neutralizing antibodies. J Virol 2004;78:6938-45.

[32] Buchholz UJ, Bukreyev A, Yang L, Lamirande EW, Murphy BR, Subbarao K, et al. Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc Natl Acad Sci U S A 2004;101:9804-9.

[33] Guan Y, Poon LL, Cheung CY, Ellis TM, Lim W, Lipatov AS, et al. H5N1 influenza: a protean pandemic threat. Proc Natl Acad Sci U S A 2004;101:8156-61.

[34] Poon LL, Guan Y, Nicholls JM, Yuen KY, Peiris JS. The aetiology, origins, and diagnosis of severe acute respiratory syndrome. Lancet Infect Dis 2004;4:663-71.

[35] Lau SK, Woo PC, Li KS, Huang Y, Tsoi HW, Wong BH, et al. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc Natl Acad Sci U S A 2005;102:14040-5.

[36] Poon LL, Chu DK, Chan KH, Wong OK, Ellis TM, Leung YH, et al. Identification of a novel coronavirus in bats. J Virol 2005;79:2001-9.

[37] Li W, Shi Z, Yu M, Ren W, Smith C, Epstein JH, et al. Bats are natural reservoirs of SARS-like coronaviruses. Science 2005;310:676-9.

[38] Enjuanes L, Dediego ML, Alvarez E, Deming D, Sheahan T, Baric R. Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease. Virus Res 2008;133:45-62.

[39] Lamirande EW, DeDiego ML, Roberts A, Jackson JP, Alvarez E, Sheahan T, et al. A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden Syrian hamsters. J Virol 2008;82:7721-4.

[40] Bridges CB, Katz JM, Levandowski RA, Cox NJ. Inactivated Influenza Vaccines. In: Plotkin SA, A. OW, A. OP, editors. Vaccines 5th ed,: Saunders-Elsevier, 2008.

[41] Girard MP, Cherian T, Pervikov Y, Kieny MP. A review of vaccine research and development: human acute respiratory infections. Vaccine 2005;23:5708-24.

[42] Kilbourne ED. Influenza pandemics: can we prepare for the unpredictable? Viral Immunol 2004;17:350-7.

[43] Lipatov AS, Govorkova EA, Webby RJ, Ozaki H, Peiris M, Guan Y, et al. Influenza: emergence and control. J Virol 2004;78:8951-9.

[44] Girard MP, Osterhaus A, Pervikov Y, Palkonyay L, Kieny MP. Report of the third meeting on "influenza vaccines that induce broad spectrum and long-lasting immune responses", World Health Organization, Geneva, Switzerland, 3-4 December 2007. Vaccine 2008;26:2443-50.

[45] Girard M, Palkonyay L, Kieny MP. Report of the 4th meeting on the "Evaluation of pandemic influenza prototype vaccines in clinical trials" World Health Organization, Geneva, Switzerland, 14-15 February 2008. Vaccine 2008.

[46] Sazawal S, Black RE. Effect of pneumonia case management on mortality in neonates, infants, and preschool children: a meta-analysis of community-based trials. Lancet Infect Dis 2003;3:547-56.

[47] Talbot TR, Poehling KA, Hartert TV, Arbogast PG, Halasa NB, Edwards KM, et al. Seasonality of invasive pneumococcal disease: temporal relation to documented influenza and respiratory syncytial viral circulation. Am J Med 2005;118:285-91.

[48] McCullers JA. Insights into the interaction between influenza virus and pneumococcus. Clin Microbiol Rev 2006;19:571-82.

[49] Brundage JF. Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Infect Dis 2006;6:303-12.

[50] Klugman KP, Madhi SA. Pneumococcal vaccines and flu preparedness. Science 2007;316:49-50.

[51] Cutts FT, Zaman SM, Enwere G, Jaffar S, Levine OS, Okoko JB, et al. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. Lancet 2005;365:1139-46.

[52] Sun K, Metzger DW. Inhibition of pulmonary antibacterial defense by interferon-gamma during recovery from influenza infection. Nat Med 2008;14:558-64.

[53] Influenza in the world. Wkly Epidemiol Rec 2004;79:385-8.

[54] Cases of influenza A (H5N1)--Thailand, 2004. MMWR Morb Mortal Wkly Rep 2004;53:100-3.

[55] Palese P. Influenza: old and new threats. Nat Med 2004;10:S82-7.

[56] Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. Jama 2003;289:179-86.

[57] Grijalva CG, Craig AS, Dupont WD, Bridges CB, Schrag SJ, Iwane MK, et al. Estimating influenza hospitalizations among children. Emerg Infect Dis 2006;12:103-9.

[58] Musher DM. How contagious are common respiratory tract infections? N Engl J Med 2003;348:1256-66.

[59] Zangwill KM, Belshe RB. Safety and efficacy of trivalent inactivated influenza vaccine in young children: a summary for the new era of routine vaccination. Pediatr Infect Dis J 2004;23:189-97.

[60] Ghendon YZ, Kaira AN, Elshina GA. The effect of mass influenza immunization in children on the morbidity of the unvaccinated elderly. Epidemiol Infect 2006;134:71-8.

[61] Viboud C, Alonso WJ, Simonsen L. Influenza in tropical regions. PLoS Med 2006;3:e89.

[62] Cox NJ, Subbarao K. Influenza. Lancet 1999;354:1277-82.

[63] Russell CA, Jones TC, Barr IG, Cox NJ, Garten RJ, Gregory V, et al. Influenza vaccine strain selection and recent studies on the global migration of seasonal influenza viruses. Vaccine 2008;26 D31-D4.

[64] Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect Dis 2006;12:9-14.

[65] Enserink M, Normile D. Infectious diseases. True numbers remain elusive in bird flu outbreak. Science 2005;307:1865.

[66] http://pandemic.influenza.com.

[67] Fedson DS. Preparing for pandemic vaccination: an international policy agenda for vaccine development. J Public Health Policy 2005;26:4-29.

[68] Morens DM, Fauci AS. The 1918 influenza pandemic: insights for the 21st century. J Infect Dis 2007;195:1018-28.

[69] Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis 2008;198:962-70.

[70] McCullers JA. Planning for an influenza pandemic: thinking beyond the virus. J Infect Dis 2008;198:945-7.

[71] Claas EC, Osterhaus AD, van Beek R, De Jong JC, Rimmelzwaan GF, Senne DA, et al. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 1998;351:472-7.

[72] Liu J, Xiao H, Lei F, Zhu Q, Qin K, Zhang XW, et al. Highly pathogenic H5N1 influenza virus infection in migratory birds. Science 2005;309:1206.

[73] Chen H, Smith GJ, Zhang SY, Qin K, Wang J, Li KS, et al. Avian flu: H5N1 virus outbreak in migratory waterfowl. Nature 2005;436:191-2.

[74] Chen Y, Trofe J, Gordon J, Du Pasquier RA, Roy-Chaudhury P, Kuroda MJ, et al. Interplay of cellular and humoral immune responses against BK virus in kidney transplant recipients with polyomavirus nephropathy. J Virol 2006;80:3495-505.

[75] Webster RG, Govorkova EA. H5N1 influenza--continuing evolution and spread. N Engl J Med 2006;355:2174-7.

[76] van den Berg T, Lambrecht B, Marche S, Steensels M, Van Borm S, Bublot M. Influenza vaccines and vaccination strategies in birds. Comp Immunol Microbiol Infect Dis 2008;31:121-65.

[77] Chen H, Smith GJ, Li KS, Wang J, Fan XH, Rayner JM, et al. Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci U S A 2006;103:2845-50.

[78] Fedson DS. Vaccine development for an imminent pandemic: why we should worry, what we must do. Hum Vaccin 2006;2:38-42.

[79] Belser JA, Blixt O, Chen LM, Pappas C, Maines TR, Van Hoeven N, et al. Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility. Proc Natl Acad Sci U S A 2008;105:7558-63.

[80] Bouvier NM, Palese P. The biology of influenza viruses. Vaccine 2008;26:D49-D53.

[81] Reid AH, Taubenberger JK, Fanning TG. Evidence of an absence: the genetic origins of the 1918 pandemic influenza virus. Nat Rev Microbiol 2004;2:909-14.

[82] Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature 2005;437:889-93.

[83] Holmes EC, Ghedin E, Miller N, Taylor J, Bao Y, St George K, et al. Whole-genome analysis of human influenza A virus reveals multiple persistent lineages and reassortment among recent H3N2 viruses. PLoS Biol 2005;3:e300.

[84] Schweiger B, Bruns L, Meixenberger K. Reassortment between human A(H3N2) viruses is an important evolutionary mechanism. Vaccine 2006;24:6683-90.

[85] Rambaut A, Pybus OG, Nelson MI, Viboud C, Taubenberger JK, Holmes EC. The genomic and epidemiological dynamics of human influenza A virus. Nature 2008;453:615-9.

[86] Crawford PC, Dubovi EJ, Castleman WL, Stephenson I, Gibbs EP, Chen L, et al. Transmission of equine influenza virus to dogs. Science 2005;310:482-5.

[87] Osterhaus AD, Rimmelzwaan GF, Martina BE, Bestebroer TM, Fouchier RA. Influenza B virus in seals. Science 2000;288:1051-3.

[88] Wiley DC, Skehel JJ. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem 1987;56:365-94.

[89] Carr CM, Kim PS. Flu virus invasion: halfway there. Science 1994;266:234-6.

[90] Colman PM, Lawrence MC. The structural biology of type I viral membrane fusion. Nat Rev Mol Cell Biol 2003;4:309-19.

[91] Swalley SE, Baker BM, Calder LJ, Harrison SC, Skehel JJ, Wiley DC. Full-length influenza hemagglutinin HA2 refolds into the trimeric low-pH-induced conformation. Biochemistry 2004;43:5902-11.

[92] Hatta M, Gao P, Halfmann P, Kawaoka Y. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001;293:1840-2.

[93] Gu J, Xie Z, Gao Z, Liu J, Korteweg C, Ye J, et al. H5N1 infection of the respiratory tract and beyond: a molecular pathology study. Lancet 2007;370:1137-45.

[94] Kuiken T, Taubenberger JK. Pathology of human influenza revisited. Vaccine 2008;26::D59-D66.

[95] Parrish CR, Kawaoka Y. The origins of new pandemic viruses: the acquisition of new host ranges by canine parvovirus and influenza A viruses. Annu Rev Microbiol 2005;59:553-86.

[96] van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA, Osterhaus AD, et al. H5N1 Virus Attachment to Lower Respiratory Tract. Science 2006;312:399.

[97] Tumpey TM, Maines TR, Van Hoeven N, Glaser L, Solorzano A, Pappas C, et al. A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science 2007;315:655-9.

[98] Yang ZY, Wei CJ, Kong WP, Wu L, Xu L, Smith DF, et al. Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity. Science 2007;317:825-8.

[99] Wasilenko JL, Lee CW, Sarmento L, Spackman E, Kapczynski DR, Suarez DL, et al. NP, PB1, and PB2 viral genes contribute to altered replication of H5N1 avian influenza viruses in chickens. J Virol 2008;82:4544-53.

[100] Li Z, Jiang Y, Jiao P, Wang A, Zhao F, Tian G, et al. The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. J Virol 2006;80:11115-23.

[101] Cauthen AN, Swayne DE, Sekellick MJ, Marcus PI, Suarez DL. Amelioration of influenza virus pathogenesis in chickens attributed to the enhanced interferon-inducing capacity of a virus with a truncated NS1 gene. J Virol 2007;81:1838-47.

[102] Hulse-Post DJ, Franks J, Boyd K, Salomon R, Hoffmann E, Yen HL, et al. Molecular changes in the polymerase genes (PA and PB1) associated with high pathogenicity of H5N1 influenza virus in mallard ducks. J Virol 2007;81:8515-24.

[103] Jiao P, Tian G, Li Y, Deng G, Jiang Y, Liu C, et al. A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. J Virol 2008;82:1146-54.

[104] Zhu Q, Yang H, Chen W, Cao W, Zhong G, Jiao P, et al. A naturally occurring deletion in its NS gene contributes to the attenuation of an H5N1 swine influenza virus in chickens. J Virol 2008;82:220-8.

[105] Mizgerd JP. Acute lower respiratory tract infection. N Engl J Med 2008;358:716-27.

[106] Nichol KL, Treanor JJ. Vaccines for seasonal and pandemic influenza. J Infect Dis 2006;194 Suppl 2:S111-8.

[107] Izurieta HS, Thompson WW, Kramarz P, Shay DK, Davis RL, DeStefano F, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med 2000;342:232-9.

[108] Hambidge SJ, Glanz JM, France EK, McClure D, Xu S, Yamasaki K, et al. Safety of trivalent inactivated influenza vaccine in children 6 to 23 months old. Jama 2006;296:1990-7.

[109] Bardiya N, Bae JH. Influenza vaccines: recent advances in production technologies. Appl Microbiol Biotechnol 2005;67:299-305.

[110] Rose GW, Cooper CL. Fluarix, inactivated split-virus influenza vaccine. Expert Opin Biol Ther 2006;6:301-10.

[111] Hovden AO, Cox RJ, Madhun A, Haaheim LR. Two doses of parenterally administered split influenza virus vaccine elicited high serum IgG concentrations which effectively limited viral shedding upon challenge in mice. Scand J Immunol 2005;62:342-52.

[112] Raviv Y, Blumenthal R, Tompkins SM, Humberd J, Hogan RJ, Viard M. Hydrophobic inactivation of influenza viruses confers preservation of viral structure with enhanced immunogenicity. J Virol 2008;82:4612-9.

[113] Goodman MJ, Nordin JD, Harper P, Defor T, Zhou X. The safety of trivalent influenza vaccine among healthy children 6 to 24 months of age. Pediatrics 2006;117:e821-6.

[114] Ohmit SE, Victor JC, Rotthoff JR, Teich ER, Truscon RK, Baum LL, et al. Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines. N Engl J Med 2006;355:2513-22.

[115] Manzoli L, Schioppa F, Boccia A, Villari P. The efficacy of influenza vaccine for healthy children: a meta-analysis evaluating potential sources of variation in efficacy estimates including study quality. Pediatr Infect Dis J 2007;26:97-106.

[116] Ohmit SE, Victor JC, Teich ER, Truscon RK, Rotthoff JR, Newton DW, et al. Prevention of symptomatic seasonal influenza in 2005-2006 by inactivated and live attenuated vaccines. J Infect Dis 2008;198:312-7.

[117] Belongia EA, Kieke BA, Donahue JG, Greenlee RT, Balish A, Foust A, et al. Effectiveness of inactivated influenza vaccines varied substantially with antigenic match from the 2004-2005 season to the 2006-2007 season. J Infect Dis 2009;199:159-67.

[118] Nichol KL, Nordin J, Mullooly J, Lask R, Fillbrandt K, Iwane M. Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly. N Engl J Med 2003;348:1322-32.

[119] Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E. Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med 2007;357:1373-81.

[120] Jansen AG, Sanders EA, Nichol KL, van Loon AM, Hoes AW, Hak E. Decline in influenza-associated mortality among Dutch elderly following the introduction of a nationwide vaccination program. Vaccine 2008;26:5567-74.

[121] Englund JA, Walter EB, Gbadebo A, Monto AS, Zhu Y, Neuzil KM. Immunization with trivalent inactivated influenza vaccine in partially immunized toddlers. Pediatrics 2006;118:e579-85.

[122] Englund JA, Walter EB, Fairchok MP, Monto AS, Neuzil KM. A comparison of 2 influenza vaccine schedules in 6- to 23-month-old children. Pediatrics 2005;115:1039-47.

[123] McElhaney JE, Hooton JW, Hooton N, Bleackley RC. Comparison of single versus booster dose of influenza vaccination on humoral and cellular immune responses in older adults. Vaccine 2005;23:3294-300.

[124] Quentin-Millet M-J. 8th WHO IVR Global Vaccine Research Forum. Paris; 2008 June.

[125] McElhaney JE, Dutz JP. Better influenza vaccines for older people: what will it take? J Infect Dis 2008;198:632-4.

[126] Holland D, Booy R, Looze FD, Eizenberg P, McDonald J, Karrasch J, et al. Intradermal Influenza Vaccine Administered Using a New Microinjection System Produces Superior Immunogenicity in Elderly Adults: A Randomized Controlled Trial. J Infect Dis 2008.

[127] Chiu SS, Peiris JS, Chan KH, Wong WH, Lau YL. Immunogenicity and safety of intradermal influenza immunization at a reduced dose in healthy children. Pediatrics 2007;119:1076-82.

[128] Stephenson I, Zambon MC, Rudin A, Colegate A, Podda A, Bugarini R, et al. Phase I evaluation of intranasal trivalent inactivated influenza vaccine with nontoxigenic Escherichia coli enterotoxin and novel biovector as mucosal adjuvants, using adult volunteers. J Virol 2006;80:4962-70.

[129] Glezen WP. Herd protection against influenza. J Clin Virol 2006;37:237-43.

[130] Schwartz B, Hinman A, Abramson J, Strikas RA, Allred N, Uyeki T, et al. Universal influenza vaccination in the United States: are we ready? Report of a meeting. J Infect Dis 2006;194 Suppl 2:S147-54.

[131] Belshe RB. Current status of live attenuated influenza virus vaccine in the US. Virus Res 2004;103:177-85.

[132] Gaglani MJ, Piedra PA, Herschler GB, Griffith ME, Kozinetz CA, Riggs MW, et al. Direct and total effectiveness of the intranasal, live-attenuated, trivalent cold-adapted influenza virus vaccine against the 2000-2001 influenza A(H1N1) and B epidemic in healthy children. Arch Pediatr Adolesc Med 2004;158:65-73.

[133] Vesikari T, Fleming DM, Aristegui JF, Vertruyen A, Ashkenazi S, Rappaport R, et al. Safety, efficacy, and effectiveness of cold-adapted influenza vaccine-trivalent against community-acquired, culture-confirmed influenza in young children attending day care. Pediatrics 2006;118:2298-312.

[134] Piedra PA, Gaglani MJ, Kozinetz CA, Herschler G, Riggs M, Griffith M, et al. Herd immunity in adults against influenza-related illnesses with use of the trivalent-live attenuated influenza vaccine (CAIV-T) in children. Vaccine 2005;23:1540-8.

[135] Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 2007;356:685-96.

[136] Ashkenazi S, Vertruyen A, Aristegui J, Esposito S, McKeith DD, Klemola T, et al. Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections. Pediatr Infect Dis J 2006;25:870-9.

[137] Fleming DM, Crovari P, Wahn U, Klemola T, Schlesinger Y, Langussis A, et al. Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma. Pediatr Infect Dis J 2006;25:860-9.

[138] Gaglani MJ, Piedra PA, Riggs M, Herschler G, Fewlass C, Glezen WP. Safety of the intranasal, trivalent, live attenuated influenza vaccine (LAIV) in children with intermittent wheezing in an open-label field trial. Pediatr Infect Dis J 2008;27:444-52.

[139] Piedra PA, Gaglani MJ, Kozinetz CA, Herschler GB, Fewlass C, Harvey D, et al. Trivalent live attenuated intranasal influenza vaccine administered during the 2003-2004 influenza type A (H3N2) outbreak provided immediate, direct, and indirect protection in children. Pediatrics 2007;120:e553-64.

[140] Block SL, Yogev R, Hayden FG, Ambrose CS, Zeng W, Walker RE. Shedding and immunogenicity of live attenuated influenza vaccine virus in subjects 5-49 years of age. Vaccine 2008;26:4940-6.

[141] Bergen R, Black S, Shinefield H, Lewis E, Ray P, Hansen J, et al. Safety of cold-adapted live attenuated influenza vaccine in a large cohort of children and adolescents. Pediatr Infect Dis J 2004;23:138-44.

[142] Vesikari T, Karvonen A, Smith HM, Dunning A, Razmpour A, Saville MK, et al. Safety and tolerability of cold-adapted influenza vaccine, trivalent, in infants younger than 6 months of age. Pediatrics 2008;121:e568-73.

[143] Ambrose CS, Yi T, Walker RE, Connor EM. Duration of protection provided by live attenuated influenza vaccine in children. Pediatr Infect Dis J 2008;27:744-8.

[144] Romanova J, Katinger D, Ferko B, Vcelar B, Sereinig S, Kuznetsov O, et al. Live cold-adapted influenza A vaccine produced in Vero cell line. Virus Res 2004;103:187-93.

[145] Forrest BD, Pride MW, Dunning AJ, Capeding MR, Chotpitayasunondh T, Tam JS, et al. Correlation of cellular immune responses with protection against culture-confirmed influenza virus in young children. Clin Vaccine Immunol 2008;15:1042-53.

[146] Fiers W, De Filette M, Birkett A, Neirynck S, Min Jou W. A "universal" human influenza A vaccine. Virus Res 2004;103:173-6.

[147] Cassetti MC, Couch R, Wood J, Pervikov Y. Report of meeting on the development of influenza vaccines with broad spectrum and long-lasting immune responses, World Health Organization, Geneva, Switzerland, 26-27 February 2004. Vaccine 2005;23:1529-33.

[148] De Filette M, Fiers W, Martens W, Birkett A, Ramne A, Lowenadler B, et al. Improved design and intranasal delivery of an M2e-based human influenza A vaccine. Vaccine 2006;24:6597-601.

[149] De Filette M, Ramne A, Birkett A, Lycke N, Lowenadler B, Min Jou W, et al. The universal influenza vaccine M2e-HBc administered intranasally in combination with the adjuvant CTA1-DD provides complete protection. Vaccine 2006;24:544-51.

[150] Eliasson DG, El Bakkouri K, Schon K, Ramne A, Festjens E, Lowenadler B, et al. CTA1-M2e-DD: a novel mucosal adjuvant targeted influenza vaccine. Vaccine 2008;26:1243-52.

[151] Song L, Nakaar V, Kavita U, Price A, Huleatt J, Tang J, et al. Efficacious recombinant influenza vaccines produced by high yield bacterial expression: a solution to global pandemic and seasonal needs. PLoS ONE 2008;3:e2257.

[152] Marshall JD, Heeke DS, Abbate C, Yee P, Van Nest G. Induction of interferon-gamma from natural killer cells by immunostimulatory CpG DNA is mediated through plasmacytoid-dendritic-cell-produced interferon-alpha and tumour necrosis factor-alpha. Immunology 2006;117:38-46.

[153] Pushko P, Tumpey TM, Bu F, Knell J, Robinson R, Smith G. Influenza virus-like particles comprised of the HA, NA, and M1 proteins of H9N2 influenza virus induce protective immune responses in BALB/c mice. Vaccine 2005;23:5751-9.

[154] Galarza JM, Latham T, Cupo A. Virus-like particle vaccine conferred complete protection against a lethal influenza virus challenge. Viral Immunol 2005;18:365-72.

[155] Quan FS, Huang C, Compans RW, Kang SM. Virus-like particle vaccine induces protective immunity against homologous and heterologous strains of influenza virus. J Virol 2007;81:3514-24.

[156] Bright RA, Carter DM, Daniluk S, Toapanta FR, Ahmad A, Gavrilov V, et al. Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin. Vaccine 2007;25:3871-8.

[157] Treanor JJ, Schiff GM, Hayden FG, Brady RC, Hay CM, Meyer AL, et al. Safety and immunogenicity of a baculovirus-expressed hemagglutinin influenza vaccine: a randomized controlled trial. Jama 2007;297:1577-82.

[158] Hoelscher MA, Garg S, Bangari DS, Belser JA, Lu X, Stephenson I, et al. Development of adenoviral-vector-based pandemic influenza vaccine against antigenically distinct human H5N1 strains in mice. Lancet 2006;367:475-81.

[159] Sutter G, Staib C. Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery. Curr Drug Targets Infect Disord 2003;3:263-71.

[160] Ge J, Deng G, Wen Z, Tian G, Wang Y, Shi J, et al. Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses. J Virol 2007;81:150-8.

[161] Freedman DO, Leder K. Influenza: changing approaches to prevention and treatment in travelers. J Travel Med 2005;12:36-44.

[162] http://www.who.int/vaccine_research/disease/influenza/flu_trials_tables/en/index.html.

[163] Treanor JJ, Campbell JD, Zangwill KM, Rowe T, Wolff M. Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine. N Engl J Med 2006;354:1343-51.

[164] Bresson JL, Perronne C, Launay O, Gerdil C, Saville M, Wood J, et al. Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial. Lancet 2006;367:1657-64.

[165] Zangwill KM, Treanor JJ, Campbell JD, Noah DL, Ryea J. Evaluation of the safety and immunogenicity of a booster (third) dose of inactivated subvirion H5N1 influenza vaccine in humans. J Infect Dis 2008;197:580-3.

[166] Stephenson I, Nicholson KG, Wood JM, Zambon MC, Katz JM. Confronting the avian influenza threat: vaccine development for a potential pandemic. Lancet Infect Dis 2004;4:499-509.

[167] Luke CJ, Subbarao K. Vaccines for pandemic influenza. Emerg Infect Dis 2006;12:66-72.

[168] Nolan TM, Richmond PC, Skeljo MV, Pearce G, Hartel G, Formica NT, et al. Phase I and II randomised trials of the safety and immunogenicity of a prototype adjuvanted inactivated split-virus influenza A (H5N1) vaccine in healthy adults. Vaccine 2008;26:4160-7.

[169] Nicholson KG, Colegate AE, Podda A, Stephenson I, Wood J, Ypma E, et al. Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza. Lancet 2001;357:1937-43.

[170] Bernstein DI, Edwards KM, Dekker CL, Belshe R, Talbot HK, Graham IL, et al. Effects of adjuvants on the safety and immunogenicity of an avian influenza H5N1 vaccine in adults. J Infect Dis 2008;197:667-75.

[171] Leroux-Roels I, Bernhard R, Gerard P, Drame M, Hanon E, Leroux-Roels G. Broad Clade 2 cross-reactive immunity induced by an adjuvanted clade 1 rH5N1 pandemic influenza vaccine. PLoS ONE 2008;3:e1665.

[172] Leroux-Roels I, Borkowski A, Vanwolleghem T, Drame M, Clement F, Hons E, et al. Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. Lancet 2007;370:580-9.

[173] Levie K, Leroux-Roels I, Hoppenbrouwers K, Kervyn AD, Vandermeulen C, Forgus S, et al. An adjuvanted, low-dose, pandemic influenza A (H5N1) vaccine candidate is safe, immunogenic, and induces cross-reactive immune responses in healthy adults. J Infect Dis 2008;198:642-9.

[174] Baldo V, Baldovin T, Floreani A, Carraro AM, Trivello R. MF59-adjuvanted influenza vaccine confers superior immunogenicity in adult subjects (18-60 years of age) with chronic diseases who are at risk of post-influenza complications. Vaccine 2007;25:3955-61.

[175] Lin J, Zhang J, Dong X, Fang H, Chen J, Su N, et al. Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1) vaccine: a phase I randomised controlled trial. Lancet 2006;368:991-7.

[176] Agger EM, Rosenkrands I, Olsen AW, Hatch G, Williams A, Kritsch C, et al. Protective immunity to tuberculosis with Ag85B-ESAT-6 in a synthetic cationic adjuvant system IC31. Vaccine 2006;24:5452-60.

[177] Ehrlich HJ, Muller M, Oh HM, Tambyah PA, Joukhadar C, Montomoli E, et al. A clinical trial of a whole-virus H5N1 vaccine derived from cell culture. N Engl J Med 2008;358:2573-84.

[178] Vajo Z, Kosa L, Szilvasy I, Pauliny Z, Bartha K, Visontay I, et al. Safety and immunogenicity of a prepandemic influenza A (H5N1) vaccine in children. Pediatr Infect Dis J 2008;27:1052-6.

[179] Suguitan AL, Jr., McAuliffe J, Mills KL, Jin H, Duke G, Lu B, et al. Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets. PLoS Med 2006;3:e360.

[180] Desheva JA, Lu XH, Rekstin AR, Rudenko LG, Swayne DE, Cox NJ, et al. Characterization of an influenza A H5N2 reassortant as a candidate for live-attenuated and inactivated vaccines against highly pathogenic H5N1 viruses with pandemic potential. Vaccine 2006;24:6859-66.

[181] Baskin CR, Bielefeldt-Ohmann H, Garcia-Sastre A, Tumpey TM, Van Hoeven N, Carter VS, et al. Functional genomic and serological analysis of the protective immune response resulting from vaccination of macaques with an NS1-truncated influenza virus. J Virol 2007;81:11817-27.

[182] Haynes JR, Dokken L, Wiley JA, Cawthon AG, Bigger J, Harmsen AG, et al. Influenza-pseudotyped Gag virus-like particle vaccines provide broad protection against highly pathogenic avian influenza challenge. Vaccine 2009;27:530-41.

[183] Gao W, Soloff AC, Lu X, Montecalvo A, Nguyen DC, Matsuoka Y, et al. Protection of mice and poultry from lethal H5N1 avian influenza virus through adenovirus-based immunization. J Virol 2006;80:1959-64.

[184] Kreijtz JH, Suezer Y, van Amerongen G, de Mutsert G, Schnierle BS, Wood JM, et al. Recombinant modified vaccinia virus Ankara-based vaccine induces protective immunity in mice against infection with influenza virus H5N1. J Infect Dis 2007;195:1598-606.

[185] Veits J, Romer-Oberdorfer A, Helferich D, Durban M, Suezer Y, Sutter G, et al. Protective efficacy of several vaccines against highly pathogenic H5N1 avian influenza virus under experimental conditions. Vaccine 2008;26:1688-96.

[186] Wang K, Holtz KM, Anderson K, Chubet R, Mahmoud W, Cox MM. Expression and purification of an influenza hemagglutinin--one step closer to a recombinant protein-based influenza vaccine. Vaccine 2006;24:2176-85.

[187] Wei CJ, Xu L, Kong WP, Shi W, Canis K, Stevens J, et al. Comparative efficacy of neutralizing antibodies elicited by recombinant hemagglutinin proteins from avian H5N1 influenza virus. J Virol 2008;82:6200-8.

[188] Falsey AR, Walsh EE. Respiratory syncytial virus infection in adults. Clin Microbiol Rev 2000;13:371-84.

[189] Mullooly JP, Bridges CB, Thompson WW, Chen J, Weintraub E, Jackson LA, et al. Influenza- and RSV-associated hospitalizations among adults. Vaccine 2007;25:846-55.

[190] Heilman CA. From the National Institute of Allergy and Infectious Diseases and the World Health Organization. Respiratory syncytial and parainfluenza viruses. J Infect Dis 1990;161:402-6.

[191] Reed G, Jewett PH, Thompson J, Tollefson S, Wright PF. Epidemiology and clinical impact of parainfluenza virus infections in otherwise healthy infants and young children < 5 years old. J Infect Dis 1997;175:807-13.

[192] Welliver RC. Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection. J Pediatr 2003;143:S112-7.

[193] Hall CB. Respiratory syncytial virus and parainfluenza virus. N Engl J Med 2001;344:1917-28.

[194] Henrickson KJ, Hoover S, Kehl KS, Hua W. National disease burden of respiratory viruses detected in children by polymerase chain reaction. Pediatr Infect Dis J 2004;23:S11-8.

[195] Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 1986;140:543-6.

[196] Silvestri M, Sabatini F, Defilippi AC, Rossi GA. The wheezy infant -- immunological and molecular considerations. Paediatr Respir Rev 2004;5 Suppl A:S81-7.

[197] Sigurs N, Gustafsson PM, Bjarnason R, Lundberg F, Schmidt S, Sigurbergsson F, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med 2005;171:137-41.

[198] Smyth RL, Openshaw PJ. Bronchiolitis. Lancet 2006;368:312-22.

[199] Cardenas S, Auais A, Piedimonte G. Palivizumab in the prophylaxis of respiratory syncytial virus infection. Expert Rev Anti Infect Ther 2005;3:719-26.

[200] Simoes EA, Groothuis JR, Carbonell-Estrany X, Rieger CH, Mitchell I, Fredrick LM, et al. Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing. J Pediatr 2007;151:34-42, e1.

[201] Puddu M, Fanos V. Respiratory syncytial virus infection and recurrent wheezing: what next? J Chemother 2007;19 Suppl 2:8-11.

[202] Zhao J, Takamura M, Yamaoka A, Odajima Y, Iikura Y. Altered eosinophil levels as a result of viral infection in asthma exacerbation in childhood. Pediatr Allergy Immunol 2002;13:47-50.

[203] Matsuse H, Hirose H, Tsuchida T, Fukahori S, Fukushima C, Mizuta Y, et al. Effects of respiratory syncytial virus infection on dendritic cells and cysteinyl leukotrienes in lung tissues of a murine model of asthma. Allergol Int 2007;56:165-9.

[204] Hirose H, Matsuse H, Fukahori S, Tsuchida T, Tomari S, Kawano T, et al. Effects of Repeated Respiratory Syncytial Virus Infections on Pulmonary Dendritic Cells in a Murine Model of Allergic Asthma. Int Arch Allergy Immunol 2008;147:197-205.

[205] Tregoning JS, Yamaguchi Y, Harker J, Wang B, Openshaw PJ. The role of T cells in the enhancement of respiratory syncytial virus infection severity during adult reinfection of neonatally sensitized mice. J Virol 2008;82:4115-24.

[206] Chin J, Magoffin RL, Shearer LA, Schieble JH, Lennette EH. Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol 1969;89:449-63.

[207] Kapikian AZ, Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE. An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol 1969;89:405-21.

[208] Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K, et al. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 1969;89:422-34.

[209] Olson MR, Varga SM. CD8 T cells inhibit respiratory syncytial virus (RSV) vaccine-enhanced disease. J Immunol 2007;179:5415-24.

[210] Castilow EM, Olson MR, Meyerholz DK, Varga SM. Differential role of gamma interferon in inhibiting pulmonary eosinophilia and exacerbating systemic disease in fusion protein-immunized mice undergoing challenge infection with respiratory syncytial virus. J Virol 2008;82:2196-207.

[211] Walsh EE, Falsey AR, Hennessey PA. Respiratory syncytial and other virus infections in persons with chronic cardiopulmonary disease. Am J Respir Crit Care Med 1999;160:791-5.

[212] Raboni SM, Nogueira MB, Tsuchiya LR, Takahashi GA, Pereira LA, Pasquini R, et al. Respiratory tract viral infections in bone marrow transplant patients. Transplantation 2003;76:142-6.

[213] Falsey AR, Walsh EE. Respiratory syncytial virus infection in elderly adults. Drugs Aging 2005;22:577-87.

[214] Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005;352:1749-59.

[215] Hall CB, Walsh EE, Long CE, Schnabel KC. Immunity to and frequency of reinfection with respiratory syncytial virus. J Infect Dis 1991;163:693-8.

[216] Nichols WG, Corey L, Gooley T, Davis C, Boeckh M. Parainfluenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral therapy, and effect on transplant outcome. Blood 2001;98:573-8.

[217] Cortez KJ, Erdman DD, Peret TC, Gill VJ, Childs R, Barrett AJ, et al. Outbreak of human parainfluenza virus 3 infections in a hematopoietic stem cell transplant population. J Infect Dis 2001;184:1093-7.

[218] Collins PL, Channock RM, Murphy BR. Respiratory syncytial virus. Philadelphia, PA: Lippincott, Williams & Wilkins, 2001.

[219] Tripp RA, Jones LP, Haynes LM, Zheng H, Murphy PM, Anderson LJ. CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein. Nat Immunol 2001;2:732-8.

[220] Tripp RA, Dakhama A, Jones LP, Barskey A, Gelfand EW, Anderson LJ. The G glycoprotein of respiratory syncytial virus depresses respiratory rates through the CX3C motif and substance P. J Virol 2003;77:6580-4.

[221] Harcourt J, Alvarez R, Jones LP, Henderson C, Anderson LJ, Tripp RA. Respiratory syncytial virus G protein and G protein CX3C motif adversely affect CX3CR1+ T cell responses. J Immunol 2006;176:1600-8.

[222] Li XQ, Fu ZF, Alvarez R, Henderson C, Tripp RA. Respiratory syncytial virus (RSV) infects neuronal cells and processes that innervate the lung by a process involving RSV G protein. J Virol 2006;80:537-40.

[223] Sullender WM. Respiratory syncytial virus genetic and antigenic diversity. Clin Microbiol Rev 2000;13:1-15, table of contents.

[224] Meyer G, Deplanche M, Schelcher F. Human and bovine respiratory syncytial virus vaccine research and development. Comp Immunol Microbiol Infect Dis 2008;31:191-225.

[225] Lamb RA, Parks GD. Paramyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM, editors. Fields Virology. Philadelphia: Lippincott, Williams & Wilkins,, 2007: 1449-90.

[226] Nishio M, Ohtsuka J, Tsurudome M, Nosaka T, Kolakofsky D. Human parainfluenza virus type 2 V protein inhibits genome replication by binding to the L protein: possible role in promoting viral fitness. J Virol 2008;82:6130-8.

[227] Polack FP, Karron RA. The future of respiratory syncytial virus vaccine development. Pediatr Infect Dis J 2004;23:S65-73.

[228] Walsh EE. Humoral, mucosal, and cellular immune response to topical immunization with a subunit respiratory syncytial virus vaccine. J Infect Dis 1994;170:345-50.

[229] Falsey AR, Walsh EE. Safety and immunogenicity of a respiratory syncytial virus subunit vaccine (PFP-2) in ambulatory adults over age 60. Vaccine 1996;14:1214-8.

[230] Falsey AR, Walsh EE. Safety and immunogenicity of a respiratory syncytial virus subunit vaccine (PFP-2) in the institutionalized elderly. Vaccine 1997;15:1130-2.

[231] Munoz FM, Piedra PA, Glezen WP. Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women. Vaccine 2003;21:3465-7.

[232] Groothuis JR, King SJ, Hogerman DA, Paradiso PR, Simoes EA. Safety and immunogenicity of a purified F protein respiratory syncytial virus (PFP-2) vaccine in seropositive children with bronchopulmonary dysplasia. J Infect Dis 1998;177:467-9.

[233] Piedra PA, Cron SG, Jewell A, Hamblett N, McBride R, Palacio MA, et al. Immunogenicity of a new purified fusion protein vaccine to respiratory syncytial virus: a multi-center trial in children with cystic fibrosis. Vaccine 2003;21:2448-60.

[234] Ison MG, Mills J, Openshaw P, Zambon M, Osterhaus A, Hayden F. Current research on respiratory viral infections: Fourth International Symposium. Antiviral Res 2002;55:227-78.

[235] Power UF, Plotnicky-Gilquin H, Huss T, Robert A, Trudel M, Stahl S, et al. Induction of protective immunity in rodents by vaccination with a prokaryotically expressed recombinant fusion protein containing a respiratory syncytial virus G protein fragment. Virology 1997;230:155-66.

[236] Power UF, Nguyen TN, Rietveld E, de Swart RL, Groen J, Osterhaus AD, et al. Safety and immunogenicity of a novel recombinant subunit respiratory syncytial virus vaccine (BBG2Na) in healthy young adults. J Infect Dis 2001;184:1456-60.

[237] Collins PL, Murphy BR. Respiratory syncytial virus: reverse genetics and vaccine strategies. Virology 2002;296:204-11.

[238] Karron RA, Wright PF, Hall SL, Makhene M, Thompson J, Burns BA, et al. A live attenuated bovine parainfluenza virus type 3 vaccine is safe, infectious, immunogenic, and phenotypically stable in infants and children. J Infect Dis 1995;171:1107-14.

[239] Karron RA, Belshe RB, Wright PF, Thumar B, Burns B, Newman F, et al. A live human parainfluenza type 3 virus vaccine is attenuated and immunogenic in young infants. Pediatr Infect Dis J 2003;22:394-405.

[240] Belshe RB, Newman FK, Tsai TF, Karron RA, Reisinger K, Roberton D, et al. Phase 2 evaluation of parainfluenza type 3 cold passage mutant 45 live attenuated vaccine in healthy children 6-18 months old. J Infect Dis 2004;189:462-70.

[241] Madhi SA, Cutland C, Zhu Y, Hackell JG, Newman F, Blackburn N, et al. Transmissibility, infectivity and immunogenicity of a live human parainfluenza type 3 virus vaccine (HPIV3cp45) among susceptible infants and toddlers. Vaccine 2006;24:2432-9.

[242] Wright PF, Karron RA, Belshe RB, Thompson J, Crowe JE, Jr., Boyce TG, et al. Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy. J Infect Dis 2000;182:1331-42.

[243] Karron RA, Wright PF, Belshe RB, Thumar B, Casey R, Newman F, et al. Identification of a recombinant live attenuated respiratory syncytial virus vaccine candidate that is highly attenuated in infants. J Infect Dis 2005;191:1093-104.

[244] Wright PF, Karron RA, Madhi SA, Treanor JJ, King JC, O'Shea A, et al. The interferon antagonist NS2 protein of respiratory syncytial virus is an important virulence determinant for humans. J Infect Dis 2006;193:573-81.

[245] Belshe RB, Newman FK, Anderson EL, Wright PF, Karron RA, Tollefson S, et al. Evaluation of combined live, attenuated respiratory syncytial virus and parainfluenza 3 virus vaccines in infants and young children. J Infect Dis 2004;190:2096-103.

[246] Lee MS, Greenberg DP, Yeh SH, Yogev R, Reisinger KS, Ward JI, et al. Antibody responses to bovine parainfluenza virus type 3 (PIV3) vaccination and human PIV3 infection in young infants. J Infect Dis 2001;184:909-13.

[247] Greenberg DP, Walker RE, Lee MS, Reisinger KS, Ward JI, Yogev R, et al. A bovine parainfluenza virus type 3 vaccine is safe and immunogenic in early infancy. J Infect Dis 2005;191:1116-22.

[248] Schmidt AC, McAuliffe JM, Huang A, Surman SR, Bailly JE, Elkins WR, et al. Bovine parainfluenza virus type 3 (BPIV3) fusion and hemagglutinin-neuraminidase glycoproteins make an important contribution to the restricted replication of BPIV3 in primates. J Virol 2000;74:8922-9.

[249] Schmidt AC, McAuliffe JM, Murphy BR, Collins PL. Recombinant bovine/human parainfluenza virus type 3 (B/HPIV3) expressing the respiratory syncytial virus (RSV) G and F proteins can be used to achieve simultaneous mucosal immunization against RSV and HPIV3. J Virol 2001;75:4594-603.

[250] Schmidt AC, Wenzke DR, McAuliffe JM, St Claire M, Elkins WR, Murphy BR, et al. Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone. J Virol 2002;76:1089-99.

[251] Tang RS, MacPhail M, Schickli JH, Kaur J, Robinson CL, Lawlor HA, et al. Parainfluenza virus type 3 expressing the native or soluble fusion (F) Protein of Respiratory Syncytial Virus (RSV) confers protection from RSV infection in African green monkeys. J Virol 2004;78:11198-207.

[252] Crowe JE, Jr., Collins PL, London WT, Chanock RM, Murphy BR. A comparison in chimpanzees of the immunogenicity and efficacy of live attenuated respiratory syncytial virus (RSV) temperature-sensitive mutant vaccines and vaccinia virus recombinants that express the surface glycoproteins of RSV. Vaccine 1993;11:1395-404.

[253] Hsu KH, Lubeck MD, Davis AR, Bhat RA, Selling BH, Bhat BM, et al. Immunogenicity of recombinant adenovirus-respiratory syncytial virus vaccines with adenovirus types 4, 5, and 7 vectors in dogs and a chimpanzee. J Infect Dis 1992;166:769-75.

[254] Voges B, Vallbracht S, Zimmer G, Bossow S, Neubert WJ, Richter K, et al. Recombinant Sendai virus induces T cell immunity against respiratory syncytial virus that is protective in the absence of antibodies. Cell Immunol 2007;247:85-94.

[255] Zhan X, Hurwitz JL, Krishnamurthy S, Takimoto T, Boyd K, Scroggs RA, et al. Respiratory syncytial virus (RSV) fusion protein expressed by recombinant Sendai virus elicits B-cell and T-cell responses in cotton rats and confers protection against RSV subtypes A and B. Vaccine 2007;25:8782-93.

[256] Zhan X, Slobod KS, Krishnamurthy S, Luque LE, Takimoto T, Jones B, et al. Sendai virus recombinant vaccine expressing hPIV-3 HN or F elicits protective immunity and combines with a second recombinant to prevent hPIV-1, hPIV-3 and RSV infections. Vaccine 2008;26:3480-8.

[257] Elliott MB, Chen T, Terio NB, Chong SY, Abdullah R, Luckay A, et al. Alphavirus replicon particles encoding the fusion or attachment glycoproteins of respiratory syncytial virus elicit protective immune responses in BALB/c mice and functional serum antibodies in rhesus macaques. Vaccine 2007;25:7132-44.

[258] Mok H, Lee S, Utley TJ, Shepherd BE, Polosukhin VV, Collier ML, et al. Venezuelan equine encephalitis virus replicon particles encoding respiratory syncytial virus surface glycoproteins induce protective mucosal responses in mice and cotton rats. J Virol 2007;81:13710-22.

[259] Greenwood BM, Weber MW, Mulholland K. Childhood pneumonia--preventing the worlds biggest killer of children. Bull World Health Organ 2007;85:502-3.

[260] Mulholland K. Childhood pneumonia mortality--a permanent global emergency. Lancet 2007;370:285-9.

[261] Black S, Eskola J, Whitney C, Shinefield H. Pneumococcal conjugate vaccine and pneumococcal common protein vaccines. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines 5th ed. Philadelphia: Saunders-Elsevier, 2008: 531-67.

[262] Black RE, Morris SS, Bryce J. Where and why are 10 million children dying every year? Lancet 2003;361:2226-34.

[263] Mulholland K. Magnitude of the problem of childhood pneumonia. Lancet 1999;354:590-2.

[264] Peltola H. Burden of meningitis and other severe bacterial infections of children in africa: implications for prevention. Clin Infect Dis 2001;32:64-75.

[265] Henrichsen J. Typing of Streptococcus pneumoniae: past, present, and future. Am J Med 1999;107:50S-4S.

[266] Hausdorff WP, Bryant J, Paradiso PR, Siber GR. Which pneumococcal serogroups cause the most invasive disease: implications for conjugate vaccine formulation and use, part I. Clin Infect Dis 2000;30:100-21.

[267] Coles CL, Kanungo R, Rahmathullah L, Thulasiraj RD, Katz J, Santosham M, et al. Pneumococcal nasopharyngeal colonization in young South Indian infants. Pediatr Infect Dis J 2001;20:289-95.

[268] Mbelle N, Huebner RE, Wasas AD, Kimura A, Chang I, Klugman KP. Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J Infect Dis 1999;180:1171-6.

[269] Decousser JW, Ovetchkine P, Collignon A, Chaplain C, Estrangin E, Fremaux A, et al. Multicentre study of the molecular epidemiology, serotypes and antimicrobial susceptibility patterns of invasive Streptococcus pneumoniae invasive isolated from children in the Ille de France area. Eur J Clin Microbiol Infect Dis 2004;23:27-33.

[270] INPES. Direction Générale de la Santé, Guide des Vaccinations. Edition 2006 ed. Saint-Denis, France, 2006.

[271] Boisier P, Mainassara HB, Sidikou F, Djibo S, Kairo KK, Chanteau S. Case-fatality ratio of bacterial meningitis in the African meningitis belt: we can do better. Vaccine 2007;25 Suppl 1:A24-9.

[272] Obaro SK. Prospects for pneumococcal vaccination in African children. Acta Trop 2000;75:141-53.

[273] Brent AJ, Ahmed I, Ndiritu M, Lewa P, Ngetsa C, Lowe B, et al. Incidence of clinically significant bacteraemia in children who present to hospital in Kenya: community-based observational study. Lancet 2006;367:482-8.

[274] Goetghebuer T, West TE, Wermenbol V, Cadbury AL, Milligan P, Lloyd-Evans N, et al. Outcome of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae type b in children in The Gambia. Trop Med Int Health 2000;5:207-13.

[275] Kaplan V, Angus DC, Griffin MF, Clermont G, Scott Watson R, Linde-Zwirble WT. Hospitalized community-acquired pneumonia in the elderly: age- and sex-related patterns of care and outcome in the United States. Am J Respir Crit Care Med 2002;165:766-72.

[276] Davidson M, Parkinson AJ, Bulkow LR, Fitzgerald MA, Peters HV, Parks DJ. The epidemiology of invasive pneumococcal disease in Alaska, 1986-1990--ethnic differences and opportunities for prevention. J Infect Dis 1994;170:368-76.

[277] Torzillo PJ, Hanna JN, Morey F, Gratten M, Dixon J, Erlich J. Invasive pneumococcal disease in central Australia. Med J Aust 1995;162:182-6.

[278] Ortqvist A, Hedlund J, Kalin M. Streptococcus pneumoniae: epidemiology, risk factors, and clinical features. Semin Respir Crit Care Med 2005;26:563-74.

[279] Hart CA, Beeching NJ, Duerden BI, Curry A, French N, Kariuki S, et al. Infections in AIDS. J Med Microbiol 2000;49:947-67.

[280] Roson B, Carratala J, Dorca J, Casanova A, Manresa F, Gudiol F. Etiology, reasons for hospitalization, risk classes, and outcomes of community-acquired pneumonia in patients hospitalized on the basis of conventional admission criteria. Clin Infect Dis 2001;33:158-65.

[281] French N, Nakiyingi J, Carpenter LM, Lugada E, Watera C, Moi K, et al. 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial. Lancet 2000;355:2106-11.

[282] Gilks CF, Ojoo SA, Ojoo JC, Brindle RJ, Paul J, Batchelor BI, et al. Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya. Lancet 1996;347:718-23.

[283] Bridy-Pappas AE, Margolis MB, Center KJ, Isaacman DJ. Streptococcus pneumoniae: description of the pathogen, disease epidemiology, treatment, and prevention. Pharmacotherapy 2005;25:1193-212.

[284] Chu C, Schneerson R, Robbins JB, Rastogi SC. Further studies on the immunogenicity of Haemophilus influenzae type b and pneumococcal type 6A polysaccharide-protein conjugates. Infect Immun 1983;40:245-56.

[285] Fiore AE, Levine OS, Elliott JA, Facklam RR, Butler JC. Effectiveness of pneumococcal polysaccharide vaccine for preschool-age children with chronic disease. Emerg Infect Dis 1999;5:828-31.

[286] Shapiro ED, Berg AT, Austrian R, Schroeder D, Parcells V, Margolis A, et al. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 1991;325:1453-60.

[287] Kumar D, Chen MH, Wong G, Cobos I, Welsh B, Siegal D, et al. A randomized, double-blind, placebo-controlled trial to evaluate the prime-boost strategy for pneumococcal vaccination in adult liver transplant recipients. Clin Infect Dis 2008;47:885-92.

[288] Mooney JD, Weir A, McMenamin J, Ritchie LD, Macfarlane TV, Simpson CR, et al. The impact and effectiveness of pneumococcal vaccination in Scotland for those aged 65 and over during winter 2003/2004. BMC Infect Dis 2008;8:53.

[289] Vila-Corcoles A. Is the pneumococcal polysaccharide vaccine effective in preventing pneumonia? Lancet Infect Dis 2008;8:405-6.

[290] Ochoa-Gondar O, Vila-Corcoles A, Ansa X, Rodriguez-Blanco T, Salsench E, de Diego C, et al. Effectiveness of pneumococcal vaccination in older adults with chronic respiratory diseases: results of the EVAN-65 study. Vaccine 2008;26:1955-62.

[291] Huss A, Scott P, Stuck AE, Trotter C, Egger M. Efficacy of pneumococcal vaccination in adults: a meta-analysis. CMAJ 2009;180:48-58.

[292] O'Brien KL, Hochman M, Goldblatt D. Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue? Lancet Infect Dis 2007;7:597-606.

[293] Lehmann D, Pomat WS, Riley ID, Alpers MP. Studies of maternal immunisation with pneumococcal polysaccharide vaccine in Papua New Guinea. Vaccine 2003;21:3446-50.

[294] Healy CM, Baker CJ. Prospects for prevention of childhood infections by maternal immunization. Curr Opin Infect Dis 2006;19:271-6.

[295] Vila-Corcoles A. Advances in pneumococcal vaccines: what are the advantages for the elderly? Drugs Aging 2007;24:791-800.

[296] de Roux A, Schmole-Thoma B, Siber GR, Hackell JG, Kuhnke A, Ahlers N, et al. Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory. Clin Infect Dis 2008;46:1015-23.

[297] Esposito S, Lizioli A, Lastrico A, Begliatti E, Rognoni A, Tagliabue C, et al. Impact on respiratory tract infections of heptavalent pneumococcal conjugate vaccine administered at 3, 5 and 11 months of age. Respir Res 2007;8:12.

[298] Vestrheim DF, Lovoll O, Aaberge IS, Caugant DA, Hoiby EA, Bakke H, et al. Effectiveness of a 2+1 dose schedule pneumococcal conjugate vaccination programme on invasive pneumococcal disease among children in Norway. Vaccine 2008;26:3277-81.

[299] Black S, Shinefield H, Fireman B, Lewis E, Ray P, Hansen JR, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr Infect Dis J 2000;19:187-95.

[300] O'Brien KL, Moulton LH, Reid R, Weatherholtz R, Oski J, Brown L, et al. Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial. Lancet 2003;362:355-61.

[301] Black SB, Cimino CO, Hansen J, Lewis E, Ray P, Corsaro B, et al. Immunogenicity and safety of measles-mumps-rubella, varicella and Haemophilus influenzae type b vaccines administered concurrently with a fourth dose of heptavalent pneumococcal conjugate vaccine compared with the vaccines administered without heptavalent pneumococcal conjugate vaccine. Pediatr Infect Dis J 2006;25:306-11.

[302] Oosterhuis-Kafeja F, Beutels P, Van Damme P. Immunogenicity, efficacy, safety and effectiveness of pneumococcal conjugate vaccines (1998-2006). Vaccine 2007;25:2194-212.

[303] Eskola J, Kilpi T, Palmu A, Jokinen J, Haapakoski J, Herva E, et al. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med 2001;344:403-9.

[304] Mahon BE, Hsu K, Karumuri S, Kaplan SL, Mason EO, Jr., Pelton SI. Effectiveness of abbreviated and delayed 7-valent pneumococcal conjugate vaccine dosing regimens. Vaccine 2006;24:2514-20.

[305] Fletcher MA, Fritzell B. Brief review of the clinical effectiveness of PREVENAR against otitis media. Vaccine 2007;25:2507-12.

[306] Benninger MS. Acute bacterial rhinosinusitis and otitis media: changes in pathogenicity following widespread use of pneumococcal conjugate vaccine. Otolaryngol Head Neck Surg 2008;138:274-8.

[307] Bliss SJ, O'Brien KL, Janoff EN, Cotton MF, Musoke P, Coovadia H, et al. The evidence for using conjugate vaccines to protect HIV-infected children against pneumococcal disease. Lancet Infect Dis 2008;8:67-80.

[308] Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R, et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 2003;348:1737-46.

[309] Azzari C, Resti M. Reduction of carriage and transmission of Streptococcus pneumoniae: the beneficial "side effect" of pneumococcal conjugate vaccine. Clin Infect Dis 2008;47:997-9.

[310] McBean AM, Park YT, Caldwell D, Yu X. Declining invasive pneumococcal disease in the U.S. elderly. Vaccine 2005;23:5641-5.

[311] Kayhty H, Auranen K, Nohynek H, Dagan R, Makela H. Nasopharyngeal colonization: a target for pneumococcal vaccination. Expert Rev Vaccines 2006;5:651-67.

[312] Madhi SA, Adrian P, Kuwanda L, Jassat W, Jones S, Little T, et al. Long-term immunogenicity and efficacy of a 9-valent conjugate pneumococcal vaccine in human immunodeficient virus infected and non-infected children in the absence of a booster dose of vaccine. Vaccine 2007;25:2451-7.

[313] Goldblatt D, Southern J, Ashton L, Richmond P, Burbidge P, Tasevska J, et al. Immunogenicity and boosting after a reduced number of doses of a pneumococcal conjugate vaccine in infants and toddlers. Pediatr Infect Dis J 2006;25:312-9.

[314] Sinha A, Levine O, Knoll MD, Muhib F, Lieu TA. Cost-effectiveness of pneumococcal conjugate vaccination in the prevention of child mortality: an international economic analysis. Lancet 2007;369:389-96.

[315] Bricks LF, Berezin E. Impact of pneumococcal conjugate vaccine on the prevention of invasive pneumococcal diseases. J Pediatr (Rio J) 2006;82:S67-74.

[316] Hausdorff WP, Siber G, Paradiso PR. Geographical differences in invasive pneumococcal disease rates and serotype frequency in young children. Lancet 2001;357:950-2.

[317] WHO, Initiative for vaccine research. What serotypes cause pneumococcal disease among children around the world? Proceedings of the 9 th Global Vaccine Research Forum Paris; 2008 June

[318] WHO, Initiative for Vaccine Research. Serotype distribution of invasive pneumococcal isolates and anti-microbial resistance patterns in south Asian countries Proceedings of the 7 th Global Vaccine Research Forum Bangkok; 2006 December

[319] Schuerman L, Prymula R, Henckaerts I, Poolman J. ELISA IgG concentrations and opsonophagocytic activity following pneumococcal protein D conjugate vaccination and relationship to efficacy against acute otitis media. Vaccine 2007;25:1962-8.

[320] Prymula R, Chlibek R, Splino M, Kaliskova E, Kohl I, Lommel P, et al. Safety of the 11-valent pneumococcal vaccine conjugated to non-typeable Haemophilus influenzae-derived protein D in the first 2 years of life and immunogenicity of the co-administered hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus, Haemophilus influenzae type b and control hepatitis A vaccines. Vaccine 2008;26:4563-70.

[321] Dagan R, Givon-Lavi N, Zamir O, Sikuler-Cohen M, Guy L, Janco J, et al. Reduction of nasopharyngeal carriage of Streptococcus pneumoniae after administration of a 9-valent pneumococcal conjugate vaccine to toddlers attending day care centers. J Infect Dis 2002;185:927-36.

[322] O'Brien KL, Millar EV, Zell ER, Bronsdon M, Weatherholtz R, Reid R, et al. Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial. J Infect Dis 2007;196:1211-20.

[323] Singleton RJ, Hennessy TW, Bulkow LR, Hammitt LL, Zulz T, Hurlburt DA, et al. Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. JAMA 2007;297:1784-92.

[324] Flannery B, Schrag S, Bennett NM, Lynfield R, Harrison LH, Reingold A, et al. Impact of childhood vaccination on racial disparities in invasive Streptococcus pneumoniae infections. Jama 2004;291:2197-203.

[325] Munoz-Almagro C, Jordan I, Gene A, Latorre C, Garcia-Garcia JJ, Pallares R. Emergence of invasive pneumococcal disease caused by nonvaccine serotypes in the era of 7-valent conjugate vaccine. Clin Infect Dis 2008;46:174-82.

[326] Barocchi MA, Censini S, Rappuoli R. Vaccines in the era of genomics: the pneumococcal challenge. Vaccine 2007;25:2963-73.

[327] Barocchi MA, Ries J, Zogaj X, Hemsley C, Albiger B, Kanth A, et al. A pneumococcal pilus influences virulence and host inflammatory responses. Proc Natl Acad Sci U S A 2006;103:2857-62.

[328] Tai SS. Streptococcus pneumoniae protein vaccine candidates: properties, activities and animal studies. Crit Rev Microbiol 2006;32:139-53.

[329] Ogunniyi AD, Grabowicz M, Briles DE, Cook J, Paton JC. Development of a vaccine against invasive pneumococcal disease based on combinations of virulence proteins of Streptococcus pneumoniae. Infect Immun 2007;75:350-7.

[330] Briles DE, Hollingshead SK, King J, Swift A, Braun PA, Park MK, et al. Immunization of humans with recombinant pneumococcal surface protein A (rPspA) elicits antibodies that passively protect mice from fatal infection with Streptococcus pneumoniae bearing heterologous PspA. J Infect Dis 2000;182:1694-701.

[331] Briles DE, Hollingshead SK, Paton JC, Ades EW, Novak L, van Ginkel FW, et al. Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae. J Infect Dis 2003;188:339-48.

[332] Hollingshead SK, Baril L, Ferro S, King J, Coan P, Briles DE. Pneumococcal surface protein A (PspA) family distribution among clinical isolates from adults over 50 years of age collected in seven countries. J Med Microbiol 2006;55:215-21.

[333] Hamel J, Charland N, Pineau I, Ouellet C, Rioux S, Martin D, et al. Prevention of pneumococcal disease in mice immunized with conserved surface-accessible proteins. Infect Immun 2004;72:2659-70.

[334] Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 1999;282:677-86.

[335] Enarson DA, Chretien J. Epidemiology of respiratory infectious diseases. Curr Opin Pulm Med 1999;5:128-35.

[336] Dye C, Espinal MA, Watt CJ, Mbiaga C, Williams BG. Worldwide incidence of multidrug-resistant tuberculosis. J Infect Dis 2002;185:1197-202.

[337] Orege PA, Fine PE, Lucas SB, Obura M, Okelo C, Okuku P. Case-control study of BCG vaccination as a risk factor for leprosy and tuberculosis in western Kenya. Int J Lepr Other Mycobact Dis 1993;61:542-9.

[338] Rodrigues LC, Diwan VK, Wheeler JG. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol 1993;22:1154-8.

[339] Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA 1994;271:698-702.

[340] Fine PE. The BCG story: lessons from the past and implications for the future. Rev Infect Dis 1989;11 Suppl 2:S353-9.

[341] Brandt L, Feino Cunha J, Weinreich Olsen A, Chilima B, Hirsch P, Appelberg R, et al. Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis. Infect Immun 2002;70:672-8.

[342] Reed SG, Alderson MR, Dalemans W, Lobet Y, Skeiky YA. Prospects for a better vaccine against tuberculosis. Tuberculosis (Edinb) 2003;83:213-9.

[343] McShane H, Pathan AA, Sander CR, Goonetilleke NP, Fletcher HA, Hill AV. Boosting BCG with MVA85A: the first candidate subunit vaccine for tuberculosis in clinical trials. Tuberculosis (Edinb) 2005;85:47-52.

[344] World Health Organization. Global Tuberculosis Control. Geneva, Switzerland; 2006.

[345] Dye C. Global epidemiology of tuberculosis. Lancet 2006;367:938-40.

[346] Smith KC, Orme IM, Starke JR. Tuberculosis vaccines. In: Plotkin SA, Orenstein WA, Offrit PA, editors. Vaccine 5th ed Saunders-Elsevier 2008: 857-85.

[347] Andrews JR, Shah NS, Gandhi N, Moll T, Friedland G. Multidrug-resistant and extensively drug-resistant tuberculosis: implications for the HIV epidemic and antiretroviral therapy rollout in South Africa. J Infect Dis 2007;196 Suppl 3:S482-90.

[348] Koenig R. Drug-resistant tuberculosis. In South Africa, XDR TB and HIV prove a deadly combination. Science 2008;319:894-7.

[349] Jain A, Mondal R. Extensively drug-resistant tuberculosis: current challenges and threats. FEMS Immunol Med Microbiol 2008;53:145-50.

[350] Shah SJ, Gheorghiade M. Heart failure with preserved ejection fraction: treat now by treating comorbidities. JAMA 2008;300:431-3.

[351] Extensively drug-resistant tuberculosis--United States, 1993-2006. MMWR Morb Mortal Wkly Rep 2007;56:250-3.

[352] Trends in tuberculosis incidence--United States, 2006. MMWR Morb Mortal Wkly Rep 2007;56:245-50.

[353] Bégué P, Denis. F, Girard MP, Frottier J. Faut-il continuer à vacciner par le BCG en France? Bull Acad Natle Med 2005;189:1305-18.

[354] Vordermeier HM, Rhodes SG, Dean G, Goonetilleke N, Huygen K, Hill AV, et al. Cellular immune responses induced in cattle by heterologous prime-boost vaccination using recombinant viruses and bacille Calmette-Guerin. Immunology 2004;112:461-70.

[355] Scanga CA, Mohan VP, Yu K, Joseph H, Tanaka K, Chan J, et al. Depletion of CD4(+) T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon gamma and nitric oxide synthase 2. J Exp Med 2000;192:347-58.

[356] Villarreal-Ramos B, McAulay M, Chance V, Martin M, Morgan J, Howard CJ. Investigation of the role of CD8+ T cells in bovine tuberculosis in vivo. Infect Immun 2003;71:4297-303.

[357] Surcel HM, Troye-Blomberg M, Paulie S, Andersson G, Moreno C, Pasvol G, et al. Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine response of blood lymphocytes to mycobacterial antigens. Immunology 1994;81:171-6.

[358] Orme IM. Prospects for new vaccines against tuberculosis. Trends Microbiol 1995;3:401-4.

[359] Park JS, Tamayo MH, Gonzalez-Juarrero M, Orme IM, Ordway DJ. Virulent clinical isolates of Mycobacterium tuberculosis grow rapidly and induce cellular necrosis but minimal apoptosis in murine macrophages. J Leukoc Biol 2006;79:80-6.

[360] Bénévolo-de-Andrade TC, Monteiro-Maia R, Cosgrove C, Castello-Branco LR. BCG Moreau Rio de Janeiro- An oral vaccine against tuberculosis-Review Mem Inst Oswaldo Cruz Rio de Janeiro 2005 100:459-65.

[361] Revised BCG vaccination guidelines for infants at risk for HIV infection. Wkly Epidemiol Rec 2007;82:193-6.

[362] Hesseling AC, Marais BJ, Gie RP, Schaaf HS, Fine PE, Godfrey-Faussett P, et al. The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children. Vaccine 2007;25:14-8.

[363] Mak TK, Hesseling AC, Hussey GD, Cotton MF. Making BCG vaccination programmes safer in the HIV era. Lancet 2008;372:786-7.

[364] Philipp WJ, Nair S, Guglielmi G, Lagranderie M, Gicquel B, Cole ST. Physical mapping of Mycobacterium bovis BCG pasteur reveals differences from the genome map of Mycobacterium tuberculosis H37Rv and from M. bovis. Microbiology 1996;142 ( Pt 11):3135-45.

[365] Mustafa AS, Cockle PJ, Shaban F, Hewinson RG, Vordermeier HM. Immunogenicity of Mycobacterium tuberculosis RD1 region gene products in infected cattle. Clin Exp Immunol 2002;130:37-42.

[366] Lewis KN, Liao R, Guinn KM, Hickey MJ, Smith S, Behr MA, et al. Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guerin attenuation. J Infect Dis 2003;187:117-23.

[367] Liu XQ, Dosanjh D, Varia H, Ewer K, Cockle P, Pasvol G, et al. Evaluation of T-cell responses to novel RD1- and RD2-encoded Mycobacterium tuberculosis gene products for specific detection of human tuberculosis infection. Infect Immun 2004;72:2574-81.

[368] Brosch R, Gordon SV, Garnier T, Eiglmeier K, Frigui W, Valenti P, et al. Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci U S A 2007;104:5596-601.

[369] Weir RE, Gorak-Stolinska P, Floyd S, Lalor MK, Stenson S, Branson K, et al. Persistence of the immune response induced by BCG vaccination. BMC Infect Dis 2008;8:9.

[370] Brewer TF, Colditz GA. Relationship between bacille Calmette-Guerin (BCG) strains and the efficacy of BCG vaccine in the prevention of tuberculosis. Clin Infect Dis 1995;20:126-35.

[371] Fine PE. Variation in protection by BCG: implications of and for heterologous immunity. Lancet 1995;346:1339-45.

[372] Doherty TM, Andersen P. Vaccines for tuberculosis: novel concepts and recent progress. Clin Microbiol Rev 2005;18:687-702.

[373] Girard MP, Fruth U, Kieny MP. A review of vaccine research and development: tuberculosis. Vaccine 2005;23:5725-31.

[374] Young D, Dye C. The development and impact of tuberculosis vaccines. Cell 2006;124:683-7.

[375] Ly LH, McMurray DN. Tuberculosis: vaccines in the pipeline. Expert Rev Vaccines 2008;7:635-50.

[376] Horwitz MA, Harth G, Dillon BJ, Maslesa-Galic S. Recombinant bacillus calmette-guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model. Proc Natl Acad Sci U S A 2000;97:13853-8.

[377] Horwitz MA. Recombinant BCG expressing Mycobacterium tuberculosis major extracellular proteins. Microbes Infect 2005;7:947-54.

[378] Hoft DF, Blazevic A, Abate G, Hanekom WA, Kaplan G, Soler JH, et al. A new recombinant bacille Calmette-Guerin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers. J Infect Dis 2008;198:1491-501.

[379] Pym AS, Brodin P, Majlessi L, Brosch R, Demangel C, Williams A, et al. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis. Nat Med 2003;9:533-9.

[380] Grode L, Seiler P, Baumann S, Hess J, Brinkmann V, Nasser Eddine A, et al. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin. J Clin Invest 2005;115:2472-9.

[381] Skeiky YA, Sadoff JC. Advances in tuberculosis vaccine strategies. Nat Rev Microbiol 2006;4:469-76.

[382] Abebe F, Bjune G. The emergence of Beijing family genotypes of Mycobacterium tuberculosis and low-level protection by bacille Calmette-Guerin (BCG) vaccines: is there a link? Clin Exp Immunol 2006;145:389-97.

[383] Guleria I, Teitelbaum R, McAdam RA, Kalpana G, Jacobs WR, Jr., Bloom BR. Auxotrophic vaccines for tuberculosis. Nat Med 1996;2:334-7.

[384] Collins DM. New tuberculosis vaccines based on attenuated strains of the Mycobacterium tuberculosis complex. Immunol Cell Biol 2000;78:342-8.

[385] Martin C, Williams A, Hernandez-Pando R, Cardona PJ, Gormley E, Bordat Y, et al. The live Mycobacterium tuberculosis phoP mutant strain is more attenuated than BCG and confers protective immunity against tuberculosis in mice and guinea pigs. Vaccine 2006;24:3408-19.

[386] Williams A, Hatch GJ, Clark SO, Gooch KE, Hatch KA, Hall GA, et al. Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis. Tuberculosis (Edinb) 2005;85:29-38.

[387] Sampson SL, Dascher CC, Sambandamurthy VK, Russell RG, Jacobs WR, Jr., Bloom BR, et al. Protection elicited by a double leucine and pantothenate auxotroph of Mycobacterium tuberculosis in guinea pigs. Infect Immun 2004;72:3031-7.

[388] Rosada RS, de la Torre LG, Frantz FG, Trombone AP, Zarate-Blades CR, Fonseca DM, et al. Protection against tuberculosis by a single intranasal administration of DNA-hsp65 vaccine complexed with cationic liposomes. BMC Immunol 2008;9:38.

[389] Andersen P. TB vaccines: progress and problems. Trends Immunol 2001;22:160-8.

[390] Izzo A, Brandt L, Lasco T, Kipnis AP, Orme I. NIH pre-clinical screening program: overview and current status. Tuberculosis (Edinb) 2005;85:25-8.

[391] Hope JC, Villarreal-Ramos B. Bovine TB and the development of new vaccines. Comp Immunol Microbiol Infect Dis 2008;31:77-100.

[392] Dillon DC, Alderson MR, Day CH, Lewinsohn DM, Coler R, Bement T, et al. Molecular characterization and human T-cell responses to a member of a novel Mycobacterium tuberculosis mtb39 gene family. Infect Immun 1999;67:2941-50.

[393] Brandt L, Elhay M, Rosenkrands I, Lindblad EB, Andersen P. ESAT-6 subunit vaccination against Mycobacterium tuberculosis. Infect Immun 2000;68:791-5.

[394] Skeiky YA, Ovendale PJ, Jen S, Alderson MR, Dillon DC, Smith S, et al. T cell expression cloning of a Mycobacterium tuberculosis gene encoding a protective antigen associated with the early control of infection. J Immunol 2000;165:7140-9.

[395] Skjot RL, Brock I, Arend SM, Munk ME, Theisen M, Ottenhoff TH, et al. Epitope mapping of the immunodominant antigen TB10.4 and the two homologous proteins TB10.3 and TB12.9, which constitute a subfamily of the esat-6 gene family. Infect Immun 2002;70:5446-53.

[396] Alderson MR, Bement T, Day CH, Zhu L, Molesh D, Skeiky YA, et al. Expression cloning of an immunodominant family of Mycobacterium tuberculosis antigens using human CD4(+) T cells. J Exp Med 2000;191:551-60.

[397] Olsen AW, Williams A, Okkels LM, Hatch G, Andersen P. Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT-6 in the aerosol guinea pig model. Infect Immun 2004;72:6148-50.

[398] Langermans JA, Doherty TM, Vervenne RA, van der Laan T, Lyashchenko K, Greenwald R, et al. Protection of macaques against Mycobacterium tuberculosis infection by a subunit vaccine based on a fusion protein of antigen 85B and ESAT-6. Vaccine 2005;23:2740-50.

[399] Dietrich J, Aagaard C, Leah R, Olsen AW, Stryhn A, Doherty TM, et al. Exchanging ESAT6 with TB10.4 in an Ag85B fusion molecule-based tuberculosis subunit vaccine: efficient protection and ESAT6-based sensitive monitoring of vaccine efficacy. J Immunol 2005;174:6332-9.

[400] Skeiky YA, Alderson MR, Ovendale PJ, Guderian JA, Brandt L, Dillon DC, et al. Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein. J Immunol 2004;172:7618-28.

[401] McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K, et al. Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med 2004;10:1240-4.

[402] Hawkridge T, Scriba TJ, Gelderbloem S, Smit E, Tameris M, Moyo S, et al. Safety and Immunogenicity of a New Tuberculosis Vaccine, MVA85A, in Healthy Adults in South Africa. J Infect Dis 2008;198:544-52.

[403] Vordermeier HM, Simsova M, Wilkinson KA, Wilkinson RJ, Hewinson RG, Sebo P, et al. Recognition of mycobacterial antigens delivered by genetically detoxified Bordetella pertussis adenylate cyclase by T cells from cattle with bovine tuberculosis. Infect Immun 2004;72:6255-61.

[404] Pathan AA, Sander CR, Fletcher HA, Poulton I, Alder NC, Beveridge NE, et al. Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: different boosting intervals and implications for efficacy trials. PLoS ONE 2007;2:e1052.

[405] Vordermeier HM, Huygen K, Singh M, Hewinson RG, Xing Z. Immune responses induced in cattle by vaccination with a recombinant adenovirus expressing Mycobacterial antigen 85A and Mycobacterium bovis BCG. Infect Immun 2006;74:1416-8.

[406] Sander C, McShane H. Translational mini-review series on vaccines: Development and evaluation of improved vaccines against tuberculosis. Clin Exp Immunol 2007;147:401-11.

[407] Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature 2005 Oct 6;437(7060):889-93.

[408] Rambaut A, Pybus OG, Nelson MI, Viboud C, Taubenberger JK, Holmes EC. The genomic and epidemiological dynamics of human influenza A virus. Nature 2008 May 29;453(7195):615-9.

[409] Smith DJ, Lapedes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, et al. Mapping the antigenic and genetic evolution of influenza virus. Science 2004 Jul 16;305(5682):371-6.

[410] Taubenberger JK, Morens DM. 1918 Influenza: the mother of all pandemics. Emerg Infect Dis 2006 Jan;12(1):15-22.

[411] Update: novel influenza A (H1N1) virus infections - worldwide, May 6, 2009. MMWR Morb Mortal Wkly Rep 2009 May 8;58(17):453-8.

[412] Scalera NM, Mossad SB. The first pandemic of the 21st century: a review of the 2009 pandemic variant influenza A (H1N1) virus. Postgrad Med 2009 Sep;121(5):43-7.

[413] Pensaert M, Ottis K, Vandeputte J, Kaplan MM, Bachmann PA. Evidence for the natural transmission of influenza A virus from wild ducts to swine and its potential importance for man. Bull World Health Organ 1981;59(1):75-8.

[414] Brown IH. The epidemiology and evolution of influenza viruses in pigs. Vet Microbiol 2000 May 22;74(1-2):29-46.

[415] Jung K, Song DS. Evidence of the co-circulation of influenza H1N1, H1N2 and H3N2 viruses in the pig population of Korea. Vet Rec 2007 Jul 21;161(3):104-5.

[416] Ghedin E, Fitch A, Boyne A, Griesemer S, DePasse J, Bera J, et al. Mixed infection and the genesis of influenza virus diversity. J Virol 2009 Sep;83(17):8832-41.

[417] Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 2009 Jul 10;325(5937):197-201.

[418] Cohen J. Pandemic influenza. Straight from the pig's mouth: swine research with swine influenzas. Science 2009 Jul 10;325(5937):140-1.

[419] Smith GJ, Bahl J, Vijaykrishna D, Zhang J, Poon LL, Chen H, et al. Dating the emergence of pandemic influenza viruses. Proc Natl Acad Sci U S A 2009 Jul 14;106(28):11709-12.

[420] Smith GJ, Vijaykrishna D, Bahl J, Lycett SJ, Worobey M, Pybus OG, et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 2009 Jun 25;459(7250):1122-5.

[421] Vallat B. Flu: no sign so far that the human pandemic is spread by pigs. Nature 2009 Aug 6;460(7256):683.

[422] Peiris JS, Poon LL, Guan Y. Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans. J Clin Virol 2009 Jul;45(3):169-73.

[423] Yang Y, Sugimoto JD, Halloran ME, Basta NE, Chao DL, Matrajt L, et al. The transmissibility and control of pandemic influenza A (H1N1) virus. Science 2009 Oct 30;326(5953):729-33.

[424] [http://www.who.int/csr/disease/swineflu/h1n1/surveillance20090710/ en/index/html ]. [cited; Available from:

[425] Strategic Advisory Group of Experts on Immunization - report of the extraordinary meeting on the influenza A (H1N1) 2009 pandemic, 7 July 2009. Wkly Epidemiol Rec 2009 Jul 24;84(30):301-4.

[426] Kwan-Gett TS, Baer A, Duchin JS. Spring 2009 H1N1 influenza outbreak in King country Washington. Disaster Med Pub Health Preparedness 2009;3:S109-S16.

[427] Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009 Jun 18;360(25):2605-15.

[428] Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009 Nov 12;361(20):1935-44.

[429] Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR Morb Mortal Wkly Rep 2009 May 22;58(19):521-4.

[430] Itoh Y, Shinya K, Kiso M, Watanabe T, Sakoda Y, Hatta M, et al. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 2009 Aug 20;460(7258):1021-5.

[431] De Groot AS, Ardito M, McClaine EM, Moise L, Martin WD. Immunoinformatic comparison of T-cell epitopes contained in novel swine-origin influenza A (H1N1) virus with epitopes in 2008-2009 conventional influenza vaccine. Vaccine 2009 Aug 4.

[432] Bright RA, Neuzil KM, Pervikov Y, Palkonyay L. WHO meeting on the role of neuraminidase in inducing protective immunity against influenza infection, Vilamoura, Portugal, September 14, 2008. Vaccine 2009 Oct 23;27(45):6366-9.

[433] Jain R, Goldman RD. Novel influenza A(H1N1): clinical presentation, diagnosis, and management. Pediatr Emerg Care 2009 Nov;25(11):791-6.

[434] Childs RA, Palma AS, Wharton S, Matrosovich T, Liu Y, Chai W, et al. Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray. Nat Biotechnol 2009 Sep;27(9):797-9.

[435] Jamieson DJ, Honein MA, Rasmussen SA, Williams JL, Swerdlow DL, Biggerstaff MS, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009 Aug 8;374(9688):451-8.

[436] Satpathy HK, Lindsay M, Kawwass JF. Novel H1N1 virus infection and pregnancy. Postgrad Med 2009 Nov;121(6):106-12.

[437] Webb SA, Pettila V, Seppelt I, Bellomo R, Bailey M, Cooper DJ, et al. Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N Engl J Med 2009 Nov 12;361(20):1925-34.

[438] Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, Hollingsworth TD, et al. Pandemic potential of a strain of influenza A (H1N1): early findings. Science 2009 Jun 19;324(5934):1557-61.

[439] Louie JK, Acosta M, Winter K, Jean C, Gavali S, Schechter R, et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA 2009 Nov 4;302(17):1896-902.

[440] Presanis AM, De Angelis D, Hagy A, Reed C, Riley S, Cooper BS, et al. The severity of pandemic H1N1 influenza in the United States, from April to July 2009: a Bayesian analysis. PLoS Med 2009 Dec;6(12):e1000207.

[441] Garske T, Legrand J, Donnelly CA, Ward H, Cauchemez S, Fraser C, et al. Assessing the severity of the novel influenza A/H1N1 pandemic. BMJ 2009;339:b2840.

[442] Nishiura H, Klinkenberg D, Roberts M, Heesterbeek JA. Early epidemiological assessment of the virulence of emerging infectious diseases: a case study of an influenza pandemic. PLoS One 2009;4(8):e6852.

[443] Bell DM, Weisfuse IB, Hernandez-Avila M, Del Rio C, Bustamante X, Rodier G. Pandemic influenza as 21st century urban public health crisis. Emerg Infect Dis 2009 Dec;15(12):1963-9.

[444] Boone SA, Gerba CP. The occurrence of influenza A virus on household and day care center fomites. J Infect 2005 Aug;51(2):103-9.

[445] Steel J, Lowen AC, Pena L, Angel M, Solorzano A, Albrecht R, et al. Live attenuated influenza viruses containing NS1 truncations as vaccine candidates against H5N1 highly pathogenic avian influenza. J Virol 2009 Feb;83(4):1742-53.

[446] Maines TR, Jayaraman A, Belser JA, Wadford DA, Pappas C, Zeng H, et al. Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice. Science 2009 Jul 24;325(5939):484-7.

[447] Kawaoka Y, Webster RG. Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells. Proc Natl Acad Sci U S A 1988 Jan;85(2):324-8.

[448] Hatta M, Gao P, Halfmann P, Kawaoka Y. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001 Sep 7;293(5536):1840-2.

[449] Neumann G, Noda T, Kawaoka Y. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 2009 Jun 18;459(7249):931-9.

[450] Tumpey TM, Garcia-Sastre A, Taubenberger JK, Palese P, Swayne DE, Basler CF. Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus. Proc Natl Acad Sci U S A 2004 Mar 2;101(9):3166-71.

[451] Vincent AL, Lager KM, Ma W, Lekcharoensuk P, Gramer MR, Loiacono C, et al. Evaluation of hemagglutinin subtype 1 swine influenza viruses from the United States. Vet Microbiol 2006 Dec 20;118(3-4):212-22.

[452] Guan Y, Shortridge KF, Krauss S, Li PH, Kawaoka Y, Webster RG. Emergence of avian H1N1 influenza viruses in pigs in China. J Virol 1996 Nov;70(11):8041-6.

[453] Van Reeth K. Avian and swine influenza viruses: our current understanding of the zoonotic risk. Vet Res 2007 Mar-Apr;38(2):243-60.

[454] Zhou NN, Senne DA, Landgraf JS, Swenson SL, Erickson G, Rossow K, et al. Genetic reassortment of avian, swine, and human influenza A viruses in American pigs. J Virol 1999 Oct;73(10):8851-6.

[455] Olsen CW. The emergence of novel swine influenza viruses in North America. Virus Res 2002 May 10;85(2):199-210.

[456] Webby RJ, Swenson SL, Krauss SL, Gerrish PJ, Goyal SM, Webster RG. Evolution of swine H3N2 influenza viruses in the United States. J Virol 2000 Sep;74(18):8243-51.

[457] Baskin CR, Bielefeldt-Ohmann H, Tumpey TM, Sabourin PJ, Long JP, Garcia-Sastre A, et al. Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus. Proc Natl Acad Sci U S A 2009 Mar 3;106(9):3455-60.

[458] Munster VJ, de Wit E, van den Brand JM, Herfst S, Schrauwen EJ, Bestebroer TM, et al. Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science 2009 Jul 24;325(5939):481-3.

[459] Enserink M. Pandemic influenza. Ferrets shed light on new virus's severity and spread. Science 2009 Jul 3;325(5936):17.

[460] Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. MMWR Morb Mortal Wkly Rep 2009 May 1;58(16):433-5.

[461] Ferguson NM, Cummings DA, Fraser C, Cajka JC, Cooley PC, Burke DS. Strategies for mitigating an influenza pandemic. Nature 2006 Jul 27;442(7101):448-52.

[462] Kieny MP, Fukuda K. The pandemic influenza vaccine challenge. Vaccine 2008 Sep 12;26 Suppl 4:D3-4.

[463] Collin N, de Radigues X. Vaccine production capacity for seasonal and pandemic (H1N1) 2009 influenza. Vaccine 2009 Aug 20;27(38):5184-6.

[464] Kieny MP, Costa A, Hombach J, Carrasco P, Pervikov Y, Salisbury D, et al. A global pandemic influenza vaccine action plan. Vaccine 2006 Sep 29;24(40-41):6367-70.

[465] Girard MP, Osterhaus A, Pervikov Y, Palkonyay L, Kieny MP. Report of the third meeting on "influenza vaccines that induce broad spectrum and long-lasting immune responses", World Health Organization, Geneva, Switzerland, 3-4 December 2007. Vaccine 2008 May 12;26(20):2443-50.

[466] Palache B, Krause R. Progress with human H5N1 vaccines: a perspective from industry. Expert Rev Vaccines 2009 Apr;8(4):391-400.

[467] Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, et al. Response after One Dose of a Monovalent Influenza A (H1N1) 2009 Vaccine -- Preliminary Report. N Engl J Med 2009 Sep 10.

[468] Zimmer SM, Burke DS. Historical perspective--Emergence of influenza A (H1N1) viruses. N Engl J Med 2009 Jul 16;361(3):279-85.

[469] [ http://www.niaid.nih.gov ; http://Clinical trials.gov ]. [cited; Available from:

[470] Plennevaux E, Sheldon E, Blatter M, Reeves-Hoche MK, Denis M. Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomised controlled phase 2 trials. Lancet 2009 Dec 15.

[471] Liang XF, Wang HQ, Wang JZ, Fang HH, Wu J, Zhu FC, et al. Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2009 Dec 15.

[472] Zhu FC, Wang H, Fang HH, Yang JG, Lin XJ, Liang XF, et al. A Novel Influenza A (H1N1) Vaccine in Various Age Groups. N Engl J Med 2009 Dec 17;361(25):2414-23.

[473] Clark TW, Pareek M, Hoschler K, Dillon H, Nicholson KG, Groth N, et al. Trial of 2009 Influenza A (H1N1) Monovalent MF59-Adjuvanted Vaccine. N Engl J Med 2009 Dec 17;361(25):2424-35.

[474] Vajo Z, Tamas F, Sinka L, Jankovics I. Safety and immunogenicity of a 2009 pandemic influenza A H1N1 vaccine when administered alone or simultaneously with the seasonal influenza vaccine for the 2009-10 influenza season: a multicentre, randomised controlled trial. Lancet 2009 Dec 15.

[475] Stone R. Swine flu outbreak. China first to vaccinate against novel H1N1 virus. Science 2009 Sep 18;325(5947):1482-3.

[476] Use of influenza A (H1N1) 2009 monovalent vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep 2009 Aug 28;58(RR-10):1-8.

[477] Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, Wilson E, et al. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med 2008 Oct 9;359(15):1555-64.

[478] Beigi RH, Wiringa AE, Bailey RR, Assi TM, Lee BY. Economic value of seasonal and pandemic influenza vaccination during pregnancy. Clin Infect Dis 2009 Dec 15;49(12):1784-92.

[479] Butler D. Regulators face tough flu-jab choices. Nature 2009 Jul 23;460(7254):446.

[480] Ekiert DC, Bhabha G, Elsliger MA, Friesen RH, Jongeneelen M, Throsby M, et al. Antibody recognition of a highly conserved influenza virus epitope. Science 2009 Apr 10;324(5924):246-51.

[481] Sui J, Hwang WC, Perez S, Wei G, Aird D, Chen LM, et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 2009 Mar;16(3):265-73.

[482] Forrest BD, Pride MW, Dunning AJ, Capeding MR, Chotpitayasunondh T, Tam JS, et al. Correlation of cellular immune responses with protection against culture-confirmed influenza virus in young children. Clin Vaccine Immunol 2008 Jul;15(7):1042-53.

[483] Chen GL, Subbarao K. Attacking the flu: neutralizing antibodies may lead to 'universal' vaccine. Nat Med 2009 Nov;15(11):1251-2.

[484] Fiers W, De Filette M, Birkett A, Neirynck S, Min Jou W. A "universal" human influenza A vaccine. Virus Res 2004 Jul;103(1-2):173-6.

[485] De Filette M, Ramne A, Birkett A, Lycke N, Lowenadler B, Min Jou W, et al. The universal influenza vaccine M2e-HBc administered intranasally in combination with the adjuvant CTA1-DD provides complete protection. Vaccine 2006 Jan 30;24(5):544-51.

[486] Song L, Nakaar V, Kavita U, Price A, Huleatt J, Tang J, et al. Efficacious recombinant influenza vaccines produced by high yield bacterial expression: a solution to global pandemic and seasonal needs. PLoS One 2008;3(5):e2257.

[487] Neirynck S, Deroo T, Saelens X, Vanlandschoot P, Jou WM, Fiers W. A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat Med 1999 Oct;5(10):1157-63.

[488] Heinen PP, Rijsewijk FA, de Boer-Luijtze EA, Bianchi AT. Vaccination of pigs with a DNA construct expressing an influenza virus M2-nucleoprotein fusion protein exacerbates disease after challenge with influenza A virus. J Gen Virol 2002 Aug;83(Pt 8):1851-9.